Nutrients

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21 pages, 1243 KiB

Open AccessArticle

Influence of the Mediterranean Diet on 25-Hydroxyvitamin D Levels in Adults

by Luigi Barrea, Giovanna Muscogiuri, Daniela Laudisio, Gabriella Pugliese, Giulia de Alteriis, Annamaria Colao and Silvia Savastano

Nutrients 2020, 12(5), 1439; https://doi.org/10.3390/nu12051439 - 16 May 2020

Cited by 39 | Viewed by 5736

Abstract

The Mediterranean diet (MD) is a dietary pattern effective in terms of prevention of obesity-related diseases, and represents the gold standard in preventive medicine, due to the synergistic action of many nutrients with antioxidant and anti-inflammatory properties. In addition, excess body weight significantly [...] Read more.

The Mediterranean diet (MD) is a dietary pattern effective in terms of prevention of obesity-related diseases, and represents the gold standard in preventive medicine, due to the synergistic action of many nutrients with antioxidant and anti-inflammatory properties. In addition, excess body weight significantly increases the risk of hypovitaminosis D, a well-recognized common feature of individuals with obesity. It is well-known that there is a clear gender difference in the adherence to the MD. The aim of this study was to investigate the association between adherence to the MD and 25-hydroxyvitamin D (25OHD) levels in adults, according to gender. Study population consisted of 617 participants; 296 were males and 321 were females, matched by age and body mass index (BMI). A validated 14-item questionnaire PREDIMED (Prevención con dieta Mediterránea) was used for the assessment of adherence to the MD. The 25OHD levels were determined by a direct competitive chemiluminescence immunoassay. Females have a higher PREDIMED score than males (7.4 ± 2.8 vs. 6.7 ± 3.1 score, p = 0.001), and according to PREDIMED categories, a greater percentage of males had low adherence to the MD compared to their female counterparts (40.2% vs. 37.1%; χ² = 8.94, p = 0.003). The 25OHD levels were higher in males than in females (18.3 ± 7.3 vs. 16.8 ± 7.8 ng/mL, p = 0.01), and a higher percentage of males had sufficient 25OHD levels (>30 ng/mL) than their female counterparts (10.5% vs. 3.4%, χ² = 10.96, p < 0.001). Stratifying the sample population according to 25OHD categories, BMI decreased and PREDIMED score increased significantly along with the increased 25OHD levels, in both males and females, respectively (p < 0.001). Looking at the bivariate correlations, PREDIMED score was positively correlated with 25OHD levels after adjusting for age and BMI, in both males (r = 0.21, p < 0.001) and females (r = 0.30, p < 0.001). At the bivariate proportional odds ratio (OR) model, 25OHD levels presented the highest OR values in the category low adherence vs. high adherence to the MD, in both genders (OR 1.21 and OR 1.31, in males and females, respectively). Receiver operator characteristic (ROC) analysis was performed to determine the cut-off values of PREDIMED scores predictive of 25OHD levels: PREDIMED score >5 in males (p < 0.001) and >7 in females (p < 0.001) could serve as thresholds for 25OHD levels above the median. The results of our study highlighted a novel positive association between adherence to the MD and 25OHD levels in both genders. Although 25OHD levels were higher in males than females, 69.7% were deficient. To the best of our knowledge, this is the first study to show that high adherence to the MD is associated with low BMI and high 25OHD levels in both genders, probably through the anti-inflammatory and anti-oxidant effects that are synergistically exerted by either MD or vitamin D on body weight. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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13 pages, 1705 KiB

Open AccessArticle

The Effects of Vitamin D Supplementation on Lipid and Inflammatory Profile of Healthy Adolescent Boys: A Randomized Controlled Trial

by Amirhossein Yarparvar, Ibrahim Elmadfa, Abolghasem Djazayery, Zahra Abdollahi, Forouzan Salehi and Ramin Heshmat

Nutrients 2020, 12(5), 1213; https://doi.org/10.3390/nu12051213 - 25 Apr 2020

Cited by 8 | Viewed by 3469

Abstract

Background: Deficiency of vitamin D, an anti-inflammatory micronutrient with some favorable effects on lipid profiles, has been found to be highly prevalent in adolescents. We aimed to investigate the effect of a school-based vitamin D supplementation regimen on the correction of vitamin D [...] Read more.

Background: Deficiency of vitamin D, an anti-inflammatory micronutrient with some favorable effects on lipid profiles, has been found to be highly prevalent in adolescents. We aimed to investigate the effect of a school-based vitamin D supplementation regimen on the correction of vitamin D deficiency as well as lipid and inflammatory profiles of healthy adolescent boys. Methods: In this randomized single-blind placebo-controlled trial, seventy-one healthy adolescent boys (age 17 years old) were recruited from one high school in Tehran, Iran, and randomly assigned to two groups. The supplement group received vitamin D pearls at a dose of 50,000 IU monthly for 6 months, this dose is indeed defined by the Ministry of Health in Iran for a potential national school-based vitamin D supplementation program. The other group was given placebo pearls for the same duration. Before and after the treatment, the serum levels of 25-hydroxy vitamin D (25(OH) D), parathyroid hormone (PTH), retinol, lead (Pb), the lipid profile and the inflammatory biomarkers were measured and compared. Results: Between-groups statistical analysis showed that a dose (50,000 IU/month) vitamin D significantly increased the serum levels of 25-hydroxyvitamin D (25 (OH) D) (p < 0.001) and decreased serum levels of PTH (p = 0.003). No significant change was observed in serum levels of retinol and Pb. Between-group analysis revealed that the serum levels of TG (P = 0.001) decreased while an increase in serum levels of HDL (p = 0.021) was observed (p < 0.05). Both the within- and between-group analysis showed that serum tumor necrosis factor receptor 2 (TNFR2) concentration declined while serum interleukin-10 (IL-10) increased in response to vitamin D supplementation (p < 0.05). Conclusion: A supplementation regimen of (50,000 IU/month) vitamin D in a context with high rates of vitamin deficiency has shown positive impacts on the serum vitamin D, lipid profile and inflammatory biomarkers in healthy adolescent boys. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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16 pages, 2135 KiB

Open AccessArticle

The Sun’s Vitamin in Adult Patients Affected by Prader–Willi Syndrome

by Luigi Barrea, Giovanna Muscogiuri, Gabriella Pugliese, Sara Aprano, Giulia de Alteriis, Carolina Di Somma, Annamaria Colao and Silvia Savastano

Nutrients 2020, 12(4), 1132; https://doi.org/10.3390/nu12041132 - 17 Apr 2020

Cited by 10 | Viewed by 3434

Abstract

Prader–Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia with progressive, severe obesity, and an increased risk of obesity-related comorbidities in adult life. Although low dietary vitamin D intake and low 25-hydroxy vitamin D (25OHD) levels are commonly reported in PWS in [...] Read more.

Prader–Willi syndrome (PWS) is a genetic disorder characterized by hyperphagia with progressive, severe obesity, and an increased risk of obesity-related comorbidities in adult life. Although low dietary vitamin D intake and low 25-hydroxy vitamin D (25OHD) levels are commonly reported in PWS in the context of bone metabolism, the association of low 25OHD levels with fat mass has not been extensively evaluated in PWS adults. The aims of this study were to investigate the following in PWS adults: (1) 25OHD levels and the dietary vitamin D intake; (2) associations among 25OHD levels with anthropometric measurements and fat mass; (3) specific cut-off values for body mass index (BMI) and fat mass predictive of the 25OHD levels. In this cross-sectional, single-center study we enrolled 30 participants, 15 PWS adults (age 19–41 years and 40% males) and 15 control subjects matched by age, sex, and BMI from the same geographical area (latitude 40° 49’ N; elevation 17 m). Fat mass was assessed using a bioelectrical impedance analysis (BIA) phase-sensitive system. The 25OHD levels were determined by a direct competitive chemiluminescence immunoassay. Dietary vitamin D intake data was collected by three-day food records. The 25OHD levels in the PWS adults were constantly lower across all categories of BMI and fat mass compared with their obese counterpart. The 25OHD levels were negatively associated with BMI (p = 0.04), waist circumference (p = 0.03), fat mass (p = 0.04), and dietary vitamin D intake (p < 0.001). During multiple regression analysis, dietary vitamin D intake was entered at the first step (p < 0.001), thus explaining 84% of 25OHD level variability. The threshold values of BMI and fat mass predicting the lowest decrease in the 25OHD levels were found at BMI ≥ 42 kg/m² (p = 0.01) and fat mass ≥ 42 Kg (p = 0.003). In conclusion, our data indicate that: (i) 25OHD levels and dietary vitamin D intake were lower in PWS adults than in the control, independent of body fat differences; (ii) 25OHD levels were inversely associated with BMI, waist circumference, and fat mass, but low dietary vitamin D intake was the major determinant of low vitamin D status in these patients; (iii) sample-specific cut-off values of BMI and fat mass might help to predict risks of the lowest 25OHD level decreases in PWS adults. The presence of trained nutritionists in the integrated care teams of PWS adults is strongly suggested in order to provide an accurate nutritional assessment and tailored vitamin D supplementations. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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10 pages, 1009 KiB

Open AccessArticle

CYP27B1 Gene Polymorphism rs10877012 in Patients Diagnosed with Colorectal Cancer

by Maria Latacz, Jadwiga Snarska, Elżbieta Kostyra, Konrad Wroński, Ewa Fiedorowicz, Huub Savelkoul, Beata Jarmołowska, Janusz Płomiński, Roman Grzybowski and Anna Cieślińska

Nutrients 2020, 12(4), 998; https://doi.org/10.3390/nu12040998 - 3 Apr 2020

Cited by 10 | Viewed by 4390

Abstract

Colorectal cancer (CRC) is the third most commonly occurring cancer worldwide. Intestinal cells are CYP27B1 gene expression sites and, as a consequence, they are capable of converting pro-vitamin D into the active paracrine and autocrine forms. It was demonstrated that rs10877012 polymorphism in [...] Read more.

Colorectal cancer (CRC) is the third most commonly occurring cancer worldwide. Intestinal cells are CYP27B1 gene expression sites and, as a consequence, they are capable of converting pro-vitamin D into the active paracrine and autocrine forms. It was demonstrated that rs10877012 polymorphism in the CYP27B1 gene influenced the circulating vitamin D level. This provided a rationale for determining the role that this polymorphism plays in the risk of developing colon cancer. In this study, we investigated the association of rs10877012 (T/G) polymorphism in the CYP27B1 gene with CRC susceptibility. The study population (n = 325) included CRC patients (n = 106) and healthy controls (n = 219). DNA was extracted from peripheral leukocytes and analyzed for the CYP27B1 polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. We found an association between the presence of the T allele at the polymorphic site (odds ratio (OR) = 2.94; 95% CI 1.77–4.86; p < 0.0001) and a decreased CRC incidence. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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10 pages, 1893 KiB

Open AccessArticle

Suppression of Parathyroid Hormone as a Proxy for Optimal Vitamin D Status: Further Analysis of Two Parallel Studies in Opposite Latitudes

by Marcela M. Mendes, Kathryn H. Hart, Susan A. Lanham-New and Patrícia B. Botelho

Nutrients 2020, 12(4), 942; https://doi.org/10.3390/nu12040942 - 28 Mar 2020

Cited by 13 | Viewed by 4190

Abstract

Optimal vitamin D status has commonly been defined as the level of 25-hydroxyvitamin D (25(OH)D) at which parathyroid hormone (PTH) concentrations would be maximally suppressed, represented by an observed minimum plateau. Previous findings indicate a large variation in this plateau, with values ranging [...] Read more.

Optimal vitamin D status has commonly been defined as the level of 25-hydroxyvitamin D (25(OH)D) at which parathyroid hormone (PTH) concentrations would be maximally suppressed, represented by an observed minimum plateau. Previous findings indicate a large variation in this plateau, with values ranging from <30 nmol/L up to 100 nmol/L. This disparity in values might be explained by differences in study design and methodology, ethnicity, age, gender and latitude. This study aimed to investigate the concentration of 25(OH)D at which PTH concentrations were suppressed in Brazilian women living in opposite latitudes (high vs. low: i.e., UK and Brazil), during wintertime. Using data from the D-SOL study (Interaction between Vitamin D Supplementation and Sunlight Exposure in Women Living in Opposite Latitudes), the association between 25(OH)D status and PTH levels were examined in 135 Brazilian women (56 living in England and 79 living in Brazil, aged 20–59 years old). Mean PTH concentrations for Brazilian women with vitamin D deficiency (<25 nmol/L) were significantly higher compared to those with vitamin D insufficiency (25–49.9 nmol/L) (p < 0.01), vitamin D adequacy (50–74.9 nmol/L) (p < 0.01) and those with optimal vitamin D status (>75 nmol/L) (p < 0.001). Regression modelling was used to investigate the relationship between serum 25(OH)D and PTH for the sample as a whole and for each group separately. A cubic model was statistically significant for the total sample (p < 0.001), whereas a linear model presented the best fit for Brazilian women living in England (p = 0.04) and there were no statistically significant models fitted for Brazilian women living in Brazil. The cubic model suggests that 25(OH)D concentrations above 70–80 nmol/L are optimal to suppress the parathyroid gland in Brazilian women. These findings contribute to a better understanding of the relationship between 25(OH)D and PTH in populations living in a low latitude location and are of great relevance for discussions regarding the estimation of optimal cut-offs for vitamin D levels in the Brazilian population as well as for other low latitude locations. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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14 pages, 2219 KiB

Open AccessArticle

The Association of Vitamin D Status with Lipid Profile and Inflammation Biomarkers in Healthy Adolescents

by Amirhossein Yarparvar, Ibrahim Elmadfa, Abolghassem Djazayery, Zahra Abdollahi and Forouzan Salehi

Nutrients 2020, 12(2), 590; https://doi.org/10.3390/nu12020590 - 24 Feb 2020

Cited by 21 | Viewed by 5387

Abstract

Background: The association between vitamin D status and inflammatory biomarkers and lipid profile is not well known, especially in adolescents. Therefore, the aim of the current study is to investigate the association of vitamin D status with serum lipids and inflammatory biomarkers, including [...] Read more.

Background: The association between vitamin D status and inflammatory biomarkers and lipid profile is not well known, especially in adolescents. Therefore, the aim of the current study is to investigate the association of vitamin D status with serum lipids and inflammatory biomarkers, including IL-10, IL-6, hsCRP, and TNFR-2, in male adolescents. Methods and materials: A sample of seventy-one high school male students, aged 17 years old, from a high school in Tehran were enrolled in the study. They were divided into four groups including group with serum vitamin D below 25 (ng/mL) (SVD < 25; n = 36), 25 and above (ng/mL) (SVD ≥ 25; n = 35), negative-hsCRP (n = 48), and positive-hsCRP (n = 23). Weight, height, body mass index, dietary intake, serum lipids, and inflammatory biomarkers, including IL-10, IL-6, hsCRP, and TNFR-2, were measured. Results: In the (SVD < 25) group, the serum level of TNFR-2 was significantly higher compared to that in the (SVD ≥ 25) group. There was a significant negative association between serum TNFR-2 and vitamin D levels in the whole sample. We found significant lower levels of IL-10 in positive-hsCRP group compared to the negative-hsCRP group. In addition, there was a significant negative correlation between the serum vitamin D level and hsCRP in both hsCRP groups. The HDL level was lower in the (SVD < 25) group compared to that in the (SVD ≥ 25) group. Finally, there was a negative correlation between the serum HDL and hsCRP levels in the positive-hsCRP subjects. Conclusion: Based on the findings it can be concluded that serum vitamin D affects HDL and inflammation status. Although serum levels of HDL and inflammation status are both predictors of metabolic syndrome and cardiovascular disease, further studies are needed to prove it, especially in adolescents. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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9 pages, 258 KiB

Open AccessArticle

Hydroxyvitamin D Serum Levels are Negatively Associated with Platelet Number in a Cohort of Subjects Affected by Overweight and Obesity

by Roberta Zupo, Fabio Castellana, Rodolfo Sardone, Luisa Lampignano, Carmen Di Noia, Silvia Savastano, Gianluigi Giannelli and Giovanni De Pergola

Nutrients 2020, 12(2), 474; https://doi.org/10.3390/nu12020474 - 13 Feb 2020

Cited by 12 | Viewed by 4129

Abstract

Background: Hypovitaminosis D and higher platelet numbers are emerging as cardiovascular risk factors, in particular in obese subjects. Methods: This observational study was aimed at investigating the relationship between platelet number and serum 25-hydroxyvitamin D (25(OH)D) levels in a cohort of individuals affected [...] Read more.

Background: Hypovitaminosis D and higher platelet numbers are emerging as cardiovascular risk factors, in particular in obese subjects. Methods: This observational study was aimed at investigating the relationship between platelet number and serum 25-hydroxyvitamin D (25(OH)D) levels in a cohort of individuals affected by overweight and obesity (body mass index (BMI) ≥ 25 Kg/m²). A sample of 341 subjects (248 women, 93 men), aged 18–71 years, taking no medication, was examined. Anthropometric, hormone, metabolic and common routine hematochemical parameters were examined and evaluated in association with platelet count and serum 25(OH)D levels. Results: Platelet numbers were inversely related to age (p < 0.04), 25(OH)D (p < 0.05) and uric acid (p < 0.04) levels, and directly associated with white blood cells (p < 0.01), Thyroid Stimulating Hormone (TSH) (p < 0.04), insulin levels (p < 0.002) and Homeostasis Model Assessment – Insulin Resistance (HOMA-IR) (p < 0.002). We applied statistical regression models to examine the relationship between platelet count (dependent variable) and parameters that had univariate associations with platelet numbers, showing that the association between platelet count and 25(OH)D was not confirmed. Moreover, vitamin D showed a negative independent association with BMI, diastolic blood pressure and serum insulin levels. Conclusions: This study indicates, for the first time, that vitamin D deficiency is associated with a parallel increase in platelet number, suggesting that higher platelet numbers may be one of the possible mechanisms leading to a greater cardiovascular risk in obese subjects. It also shows that vitamin D deficiency, a common condition in obesity, has independent associations with higher BMI, diastolic blood pressure and serum insulin levels. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

13 pages, 1335 KiB

Open AccessFeature PaperArticle

Vitamin D Supplementation Improves Adipose Tissue Inflammation and Reduces Hepatic Steatosis in Obese C57BL/6J Mice

by Alexandra Marziou, Clothilde Philouze, Charlène Couturier, Julien Astier, Philippe Obert, Jean-François Landrier and Catherine Riva

Nutrients 2020, 12(2), 342; https://doi.org/10.3390/nu12020342 - 28 Jan 2020

Cited by 50 | Viewed by 5114

Abstract

The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect [...] Read more.

The beneficial effect of vitamin D (VD) supplementation on body weight gain limitation and inflammation has been highlighted in primary prevention mice models, but the long-term effect of VD supplementation in tertiary prevention has never been reported in obesity models. The curative effect of VD supplementation on obesity and associated disorders was evaluated in high-fat- and high-sucrose (HFS)-fed mice. Morphological, histological, and molecular phenotype were characterized. The increased body mass and adiposity caused by HFS diet as well as fat cell hypertrophy and glucose homeostasis were not improved by VD supplementation. However, VD supplementation led to a decrease of HFS-induced inflammation in inguinal adipose tissue, characterized by a decreased expression of chemokine mRNA levels. Moreover, a protective effect of VD on HFS-induced hepatic steatosis was highlighted by a decrease of lipid droplets and a reduction of triglyceride accumulation in the liver. This result was associated with a significant decrease of gene expression coding for key enzymes involved in hepatic de novo lipogenesis and fatty acid oxidation. Altogether, our results show that VD supplementation could be of interest to blunt the adipose tissue inflammation and hepatic steatosis and could represent an interesting nutritional strategy to fight obesity-associated comorbidities. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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17 pages, 2665 KiB

Open AccessArticle

Low Levels of Vitamin D Promote Memory B Cells in Lupus

by Erin A. Yamamoto, Jane K. Nguyen, Jessica Liu, Emma Keller, Nicole Campbell, Cun-Jin Zhang, Howard R. Smith, Xiaoxia Li and Trine N Jørgensen

Nutrients 2020, 12(2), 291; https://doi.org/10.3390/nu12020291 - 22 Jan 2020

Cited by 27 | Viewed by 6259

Abstract

Background: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies have utilized lupus models to understand the mechanism underlying this relationship. The Act1-/- mouse is a spontaneous model [...] Read more.

Background: Vitamin D deficiency is a known risk factor for Systemic Lupus Erythematosus (SLE), yet clinical trials have not demonstrated efficacy and few studies have utilized lupus models to understand the mechanism underlying this relationship. The Act1-/- mouse is a spontaneous model of lupus and Sjögren’s syndrome, characterized by increased Th17 cells and peripheral B cell expansion. Vitamin D3 has anti-inflammatory properties, reduces Th17 cells and impairs B cell differentiation/activation. Therefore, we assessed how varying amounts of vitamin D3 affected lupus-like disease in the Act1-/- mouse. Methods: Act1-/- mice were fed either low/restricted (0 IU/kg), normal (2 IU/kg), or high/supplemented (10 IU/kg) vitamin D3 chow for 9 weeks, after which lupus-like features were analyzed. Results: While we found no differences in Th17 cells between vitamin D3 groups, vitamin D3 restriction specifically promoted memory B cell development, accompanied by elevated levels of serum IgM, IgG1, IgG3, and anti-dsDNA IgG. A similar significant negative association between serum vitamin D and memory B cells was confirmed in a cohort of SLE patients. Conclusion: Low levels of vitamin D3 are associated with elevated levels of memory B cells in an animal model of lupus and well-controlled SLE patients. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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Review

Jump to: Research

25 pages, 790 KiB

Open AccessReview

Vitamin D-Induced Molecular Mechanisms to Potentiate Cancer Therapy and to Reverse Drug-Resistance in Cancer Cells

by Mariarosaria Negri, Annalisa Gentile, Cristina de Angelis, Tatiana Montò, Roberta Patalano, Annamaria Colao, Rosario Pivonello and Claudia Pivonello

Nutrients 2020, 12(6), 1798; https://doi.org/10.3390/nu12061798 - 17 Jun 2020

Cited by 93 | Viewed by 9006

Abstract

Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human [...] Read more.

Increasing interest in studying the role of vitamin D in cancer has been provided by the scientific literature during the last years, although mixed results have been reported. Vitamin D deficiency has been largely associated with various types of solid and non-solid human cancers, and the almost ubiquitous expression of vitamin D receptor (VDR) has always led to suppose a crucial role of vitamin D in cancer. However, the association between vitamin D levels and the risk of solid cancers, such as colorectal, prostate and breast cancer, shows several conflicting results that raise questions about the use of vitamin D supplements in cancer patients. Moreover, studies on vitamin D supplementation do not always show improvements in tumor progression and mortality risk, particularly for prostate and breast cancer. Conversely, several molecular studies are in agreement about the role of vitamin D in inhibiting tumor cell proliferation, growth and invasiveness, cell cycle arrest and inflammatory signaling, through which vitamin D may also regulate cancer microenvironment through the activation of different molecular pathways. More recently, a role in the regulation of cancer stem cells proliferation and short non-coding microRNA (miRNAs) expression has emerged, conferring to vitamin D a more crucial role in cancer development and progression. Interestingly, it has been shown that vitamin D is able not only to potentiate the effects of traditional cancer therapy but can even contribute to overcome the molecular mechanisms of drug resistance—often triggering tumor-spreading. At this regard, vitamin D can act at various levels through the regulation of growth of cancer stem cells and the epithelial–mesenchymal transition (EMT), as well as through the modulation of miRNA gene expression. The current review reconsiders epidemiological and molecular literature concerning the role of vitamin D in cancer risk and tumor development and progression, as well as the action of vitamin D supplementation in potentiating the effects of drug therapy and overcoming the mechanisms of resistance often triggered during cancer therapies, by critically addressing strengths and weaknesses of available data from 2010 to 2020. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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17 pages, 282 KiB

Open AccessReview

Possible Role of Vitamin D in Celiac Disease Onset

by Giorgia Vici, Dalia Camilletti and Valeria Polzonetti

Nutrients 2020, 12(4), 1051; https://doi.org/10.3390/nu12041051 - 10 Apr 2020

Cited by 23 | Viewed by 6446

Abstract

Beside skeletal system maintenance and protection, possible extra-calcium roles of vitamin D have been recently described. In particular, studies have investigated possible roles of vitamin D as a key modulator of inflammation and immune mechanisms and of the intestinal mucosa barrier. In this [...] Read more.

Beside skeletal system maintenance and protection, possible extra-calcium roles of vitamin D have been recently described. In particular, studies have investigated possible roles of vitamin D as a key modulator of inflammation and immune mechanisms and of the intestinal mucosa barrier. In this regard, vitamin D has been considered as a factor that affects different conditions such as immune-mediated diseases. The new emerging role of vitamin D and its involvement in immune modulation has led it to be considered as a possible key factor involved in celiac disease (CD) onset. CD is a chronic immune-mediated enteropathy of the small intestine that is triggered by dietary gluten protein exposure in individuals who are genetically predisposed. However, along with gluten, other environmental factors are also involved in CD onset. The renewed interest in a molecule that offers great possibilities for new roles has led to an increase in studies, although there remains a lack of studies aimed at contextualizing the role of vitamin D on CD. This review aims to define the possible role of vitamin D in CD onset as it is presently understood, taking into account potential links among vitamin D, the immune system and CD. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

22 pages, 1699 KiB

Open AccessReview

Bone Metabolism and Vitamin D Implication in Gastroenteropancreatic Neuroendocrine Tumors

by Barbara Altieri, Carla Di Dato, Roberta Modica, Filomena Bottiglieri, Antonella Di Sarno, James F.H. Pittaway, Chiara Martini, Antongiulio Faggiano and Annamaria Colao

Nutrients 2020, 12(4), 1021; https://doi.org/10.3390/nu12041021 - 8 Apr 2020

Cited by 19 | Viewed by 6138

Abstract

Patients affected by gastroenteropancreatic–neuroendocrine tumors (GEP–NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including [...] Read more.

Patients affected by gastroenteropancreatic–neuroendocrine tumors (GEP–NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP–NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP–NET, focusing on vitamin D and its role in GEP–NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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36 pages, 705 KiB

Open AccessReview

Role of Vitamin D in Preventing and Treating Selected Extraskeletal Diseases—An Umbrella Review

by Friederike Maretzke, Angela Bechthold, Sarah Egert, Jana B. Ernst, Debora Melo van Lent, Stefan Pilz, Jörg Reichrath, Gabriele I. Stangl, Peter Stehle, Dorothee Volkert, Michael Wagner, Julia Waizenegger, Armin Zittermann and Jakob Linseisen

Nutrients 2020, 12(4), 969; https://doi.org/10.3390/nu12040969 - 31 Mar 2020

Cited by 74 | Viewed by 13738

Abstract

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current [...] Read more.

Evidence is accumulating that vitamin D may have beneficial effects on respiratory tract, autoimmune, neuro-degenerative, and mental diseases. The present umbrella review of systematic reviews (SRs) of cohort studies and randomised controlled trials (RCTs), plus single Mendelian randomisation studies aims to update current knowledge on the potential role of vitamin D in preventing and treating these extraskeletal diseases. Altogether, 73 SRs were identified. Observational data on primary prevention suggest an inverse association between vitamin D status and the risk of acute respiratory tract infections (ARI), dementia and cognitive decline, and depression, whereas studies regarding asthma, multiple sclerosis (MS), and type 1 diabetes mellitus (T1DM) are scarce. SRs of RCTs support observational data only for the risk of ARI. No respective RCTs are available for the prevention of chronic obstructive pulmonary disease (COPD), MS, and T1DM. SRs of RCTs indicate beneficial therapeutic effects in vitamin D-deficient patients with asthma and COPD, while effects on major depression and T1DM need to be further elucidated. Mendelian randomisation studies do not consistently support the results of SRs. Since several limitations of the included SRs and existing RCTs do not permit definitive conclusions regarding vitamin D and the selected diseases, further high-quality RCTs are warranted. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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22 pages, 1986 KiB

Open AccessReview

Single Nucleotide Polymorphisms in 25-Hydroxyvitamin D3 1-Alpha-Hydroxylase (CYP27B1) Gene: The Risk of Malignant Tumors and Other Chronic Diseases

by Maria Latacz, Jadwiga Snarska, Elżbieta Kostyra, Ewa Fiedorowicz, Huub F. J. Savelkoul, Roman Grzybowski and Anna Cieślińska

Nutrients 2020, 12(3), 801; https://doi.org/10.3390/nu12030801 - 18 Mar 2020

Cited by 21 | Viewed by 6651

Abstract

Vitamin D is widely known for its roles in the promotion of apoptosis and differentiation, with simultaneous inhibition of proliferation, inflammation, angiogenesis, invasion, and metastasis. Modern literature lacks complete information on polymorphisms in CYP27B1, the only enzyme capable of vitamin D activation. [...] Read more.

Vitamin D is widely known for its roles in the promotion of apoptosis and differentiation, with simultaneous inhibition of proliferation, inflammation, angiogenesis, invasion, and metastasis. Modern literature lacks complete information on polymorphisms in CYP27B1, the only enzyme capable of vitamin D activation. This review presents gathered data that relate to genetic variants in CYP27B1 gene in correlation to multiple diseases, mostly concerning colorectal, prostate, breast, lung, and pancreatic cancers, as well as on other pathologies, such as non-Hodgkin’s lymphoma, oral lichen planus, or multiple sclerosis. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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30 pages, 2608 KiB

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Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

by Mattia Bellan, Laura Andreoli, Chiara Mele, Pier Paolo Sainaghi, Cristina Rigamonti, Silvia Piantoni, Carla De Benedittis, Gianluca Aimaretti, Mario Pirisi and Paolo Marzullo

Nutrients 2020, 12(3), 789; https://doi.org/10.3390/nu12030789 - 17 Mar 2020

Cited by 49 | Viewed by 10491

Abstract

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly [...] Read more.

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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11 pages, 240 KiB

Open AccessReview

Vitamin D Supplementation in Multiple Sclerosis: A Critical Analysis of Potentials and Threats

by Julia Feige, Tobias Moser, Lara Bieler, Kerstin Schwenker, Larissa Hauer and Johann Sellner

Nutrients 2020, 12(3), 783; https://doi.org/10.3390/nu12030783 - 16 Mar 2020

Cited by 93 | Viewed by 14078

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in [...] Read more.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS). In recent years, vitamin D has gained attention, as low serum levels are suspected to increase the risk for MS. Cholecalciferol supplementation has been tested in several clinical trials, since hypovitaminosis D was linked to higher disease activity and may even play a role in long-term outcome. Here, we review the current understanding of the molecular effects of vitamin D beyond calcium homeostasis, the potential beneficial action in MS and hazards including complications of chronic and high-dose therapy. In clinical trials, doses of up to 40,000 IU/day were tested and appeared safe as add-on therapy for short-term periods. A recent meta-analysis of a randomized, double-blind, placebo-controlled clinical trial investigating vitamin D as add-on therapy in MS, however, suggested that vitamin D had no therapeutic effect on disability or relapse rate. We recognize a knowledge gap for chronic and high-dose therapy, which can lead to life-threatening complications related to vitamin D toxicity including renal failure, cardiac arrythmia and status epilepticus. Moreover, vitamin D toxicity may manifest as fatigue, muscle weakness or urinary dysfunction, which may mimic the natural course of progressive MS. Given these limitations, vitamin D supplementation in MS is a sensitive task which needs to be supervised by physicians. While there is strong evidence for vitamin D deficiency and the development of MS, the risk-benefit profile of dosage and duration of add-on supplementation needs to be further clarified. Full article

(This article belongs to the Special Issue The Role of Vitamin D in Chronic Diseases)

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